Limits...
Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.

Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V - J. Cell Biol. (2003)

Bottom Line: The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming.We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs.These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.

ABSTRACT
Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.

Show MeSH

Related in: MedlinePlus

Developmental and anatomical distribution of NeuN+/CNP-GFP+ neurons in the postnatal hippocampus. The anatomical distribution of NeuN+/CNP-GFP+ cells was analyzed in Z-series confocal scanning images (20–32 μm of thickness, step size = 0.5 μm between successive images of the same field) from P6 (A and C) and P30 (B and D) hippocampus. Square fields of 228 μm2 were separately acquired in CA1, CA3, and the dentate gyrus (DG). We calculated the absolute density of total CNP-GFP+ cells and NeuN+/CNP-GFP+ cells in each area at P6 (A) and P30 (B). We found developmental changes in the percentage of NeuN+/CNP-GFP+ cells within the CNP-GFP+ population only in CA1 between P6 (C) and P30 (D). Histogram values represent mean ± SEM (total GFP+ cells counted = 841, two independent experiments). Statistical data pointed out in B were derived from the comparison of each P30 experimental parameter with its identical counterpart at P6. ***, P < 0.001; *, P < 0.05 (t test).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172886&req=5

fig7: Developmental and anatomical distribution of NeuN+/CNP-GFP+ neurons in the postnatal hippocampus. The anatomical distribution of NeuN+/CNP-GFP+ cells was analyzed in Z-series confocal scanning images (20–32 μm of thickness, step size = 0.5 μm between successive images of the same field) from P6 (A and C) and P30 (B and D) hippocampus. Square fields of 228 μm2 were separately acquired in CA1, CA3, and the dentate gyrus (DG). We calculated the absolute density of total CNP-GFP+ cells and NeuN+/CNP-GFP+ cells in each area at P6 (A) and P30 (B). We found developmental changes in the percentage of NeuN+/CNP-GFP+ cells within the CNP-GFP+ population only in CA1 between P6 (C) and P30 (D). Histogram values represent mean ± SEM (total GFP+ cells counted = 841, two independent experiments). Statistical data pointed out in B were derived from the comparison of each P30 experimental parameter with its identical counterpart at P6. ***, P < 0.001; *, P < 0.05 (t test).

Mentions: NeuN+/CNP-GFP+ cells were not only observed at early postnatal stages, but also in the adult hippocampus (P30). In all hippocampal regions, but particularly in CA1 and CA3, we observed that the absolute density of NeuN+/CNP-GFP+ cells and the total number of CNP-GFP+ cells decreased during postnatal maturation, between P6 and P30 (Fig. 7, A and B) . At P30, the density of NeuN+/CNP-GFP+ cells followed a clear anatomical gradient: dentate gyrus > CA3 > CA1 (Fig. 7 B). In parallel, total CNP-GFP+ cells were distributed according to the same gradient (Fig. 7 B). Finally, except in CA1, the percentage of CNP-GFP+ cells that expressed NeuN in the hippocampus remained constant between P6 and P30, and was maximal in the dentate gyrus (Fig. 7, C and D). These findings suggest that the intrinsic neurogenic potential of CNP-GFP+ cells in CA3 and dentate gyrus may not decrease in adulthood. These results could also indicate that the decrease in the absolute number of multipotent CNP-GFP+ cells might underlie the reduction of newly formed NeuN+/CNP-GFP+ neurons in the adult hippocampus.


Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.

Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V - J. Cell Biol. (2003)

Developmental and anatomical distribution of NeuN+/CNP-GFP+ neurons in the postnatal hippocampus. The anatomical distribution of NeuN+/CNP-GFP+ cells was analyzed in Z-series confocal scanning images (20–32 μm of thickness, step size = 0.5 μm between successive images of the same field) from P6 (A and C) and P30 (B and D) hippocampus. Square fields of 228 μm2 were separately acquired in CA1, CA3, and the dentate gyrus (DG). We calculated the absolute density of total CNP-GFP+ cells and NeuN+/CNP-GFP+ cells in each area at P6 (A) and P30 (B). We found developmental changes in the percentage of NeuN+/CNP-GFP+ cells within the CNP-GFP+ population only in CA1 between P6 (C) and P30 (D). Histogram values represent mean ± SEM (total GFP+ cells counted = 841, two independent experiments). Statistical data pointed out in B were derived from the comparison of each P30 experimental parameter with its identical counterpart at P6. ***, P < 0.001; *, P < 0.05 (t test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172886&req=5

fig7: Developmental and anatomical distribution of NeuN+/CNP-GFP+ neurons in the postnatal hippocampus. The anatomical distribution of NeuN+/CNP-GFP+ cells was analyzed in Z-series confocal scanning images (20–32 μm of thickness, step size = 0.5 μm between successive images of the same field) from P6 (A and C) and P30 (B and D) hippocampus. Square fields of 228 μm2 were separately acquired in CA1, CA3, and the dentate gyrus (DG). We calculated the absolute density of total CNP-GFP+ cells and NeuN+/CNP-GFP+ cells in each area at P6 (A) and P30 (B). We found developmental changes in the percentage of NeuN+/CNP-GFP+ cells within the CNP-GFP+ population only in CA1 between P6 (C) and P30 (D). Histogram values represent mean ± SEM (total GFP+ cells counted = 841, two independent experiments). Statistical data pointed out in B were derived from the comparison of each P30 experimental parameter with its identical counterpart at P6. ***, P < 0.001; *, P < 0.05 (t test).
Mentions: NeuN+/CNP-GFP+ cells were not only observed at early postnatal stages, but also in the adult hippocampus (P30). In all hippocampal regions, but particularly in CA1 and CA3, we observed that the absolute density of NeuN+/CNP-GFP+ cells and the total number of CNP-GFP+ cells decreased during postnatal maturation, between P6 and P30 (Fig. 7, A and B) . At P30, the density of NeuN+/CNP-GFP+ cells followed a clear anatomical gradient: dentate gyrus > CA3 > CA1 (Fig. 7 B). In parallel, total CNP-GFP+ cells were distributed according to the same gradient (Fig. 7 B). Finally, except in CA1, the percentage of CNP-GFP+ cells that expressed NeuN in the hippocampus remained constant between P6 and P30, and was maximal in the dentate gyrus (Fig. 7, C and D). These findings suggest that the intrinsic neurogenic potential of CNP-GFP+ cells in CA3 and dentate gyrus may not decrease in adulthood. These results could also indicate that the decrease in the absolute number of multipotent CNP-GFP+ cells might underlie the reduction of newly formed NeuN+/CNP-GFP+ neurons in the adult hippocampus.

Bottom Line: The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming.We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs.These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.

ABSTRACT
Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.

Show MeSH
Related in: MedlinePlus